Multicenter Phase I/II Study of Nivolumab Combined with Paclitaxel Plus Ramucirumab as Second-line Treatment in Patients with Advanced Gastric Cancer

Purpose: We conducted a phase I/II study to investigate the safety and efficacy of nivolumab with paclitaxel plus ramucirumab. Patients and Methods: Patients with advanced gastric cancer (AGC) refractory to first-line chemotherapy were included. Patients received nivolumab (3 mg/kg on days 1 and 15) combined with paclitaxel (80 mg/m2 on days 1, 8, and 15) and ramucirumab (8 mg/kg on days 1 and 15) every 4 weeks. After feasibility evaluation in six patients (phase I), 37 additional patients were enrolled in the phase II part with the primary endpoint of 6-month progression-free survival (PFS) rate with two-sided 80% confidence interval (CI). The combined positive score (CPS) was defined as the number of programmed death-ligand 1–positive cells divided by the total number of viable tumor cells multiplied by 100. Results: Forty-three patients were enrolled. Of these, 60.5% had CPS ≥ 1. Dose-limiting toxicities were observed in two patients, and the recommended dose was determined as level 1. Thirty-nine (90.7%) patients experienced treatment-related adverse events (AEs) grade ≥3 and 14 (32.6%) patients experienced immune-related AEs grade ≥3. The overall response rate was 37.2% (95% CI, 23.0%–53.5%) and the 6-month PFS rate was 46.5% (80% CI, 36.4%–55.8%; P = 0.067). Median survival time was 13.1 months (95% CI, 8.0–16.6 months): 13.8 months (95% CI, 8.0–19.5 months) in patients with CPS ≥ 1 and 8.0 months (95% CI, 4.8–24.1 months) in patients with CPS < 1. Conclusions: Nivolumab with paclitaxel plus ramucirumab demonstrated promising antitumor activity with manageable toxicities as second-line treatment for AGC.